The long-term objective of this proposal is to determine the mechanism by which exercise produces airway obstruction in asthmatics. The attraction of studying this aspect of asthma is that exercise is a potent, naturally occurring stimulus that is potentially operational in the everyday life of all people with this illness. Thus, if one could unravel the manner in which exercise produces airway obstruction, it may be possible to gain great insights into the pathophysiology of asthma in general and ultimately into mechanisms for its control. The proposed studies are designed to: (1) to examine, in greater depth, the role of the bronchial microvasculature in the development of EIA; (2) to determine if mediators of immediate hypersensitivity are released with thermal challenges and if they play a role in producing the obstructive response; (3) to further explore the mechanism for the refractory period; and (4) to examine the relationship between the airway obstruction produced by ultrasonic aerosols and thermal challenges. To achieve the first goal, a group of asthmatics will perform standard isocapnic hyperventilation stimulus-response curves while breathing cold, room, body condition, and hot dry air. On other occasion they will undergo bronchoscopy with insertion of a thermal probe and will repeat the above challenges, in all particulars while airstream temperatures are recorded continuously from the mouth to the peripheral airways during hyperpnea and recovery. These data will permit a systemation evaluation of the variables that are believed to be important in the pathogenesis of EIA. In the second set of studies a blinded multicenter trial will be undertaken in which multiple mediators will be measured in blood and bronchoalveolar fluid with exercise and compared with antigen. The third goal will be obtained by determining if repetitive exercise slows the rate of airway rewarming and if this phenomenon can be offset by increasing the end-challenge thermal gradient. To see if the release of catecholamines plays a part in this response, the study will be repeated using isocapnic hypercapnic hyperventilation. This stimulus produces the same thermal effects exercise, but does so without an increase in circulating catecholamines. The final aim will be accomplished by having asthmatics undergo an exercise bronchoprovocation while airstream temperatures are recorded. Surface osmolarities will be calculated from these data. On another day the subjects will inhale sufficient quantities of 3% saline to produce the same degree of obstruction and the changes in osmolarity with this challenge will be compared with that induced with exercise.